Factors Related to Major Bleeding After Ticagrelor Therapy: Results from the TICO Trial
Key result
Ticagrelor monotherapy after 3-month DAPT cuts net adverse clinical events ~41% in high-risk ACS.
- HR 0.59
- 95% CI 0.39-0.90
- P interaction = 0.74
- n=2,660
Figures
Why the study?
Data are lacking on factors related to clinically relevant bleeding following ticagrelor treatment after coronary stent implantation for acute coronary syndrome.
Does 3-month aspirin therapy with continued ticagrelor reduce net adverse clinical events compared to 12-month dual antiplatelet therapy in ACS patients undergoing PCI?
Key Points
- To identify clinical and procedural predictors of major bleeding in acute coronary syndrome patients receiving ticagrelor after coronary stenting.
- In this analysis from the TICO randomized trial (NCT02494895), 2660 patients treated with ticagrelor after new-generation sirolimus-eluting stent implantation for acute coronary syndrome were analyzed.
- Patients with major bleeding, defined by TIMI major or BARC type 3 or 5 criteria within 12 months, were compared with non-bleeding patients to evaluate predictors and the effect of 3-month versus 12-month aspirin therapy.
- Within 12 months, TIMI major bleeding occurred in 54 patients (2.0%) and BARC type 3/5 bleeding occurred in 97 patients (3.6%).
- Independent risk factors for TIMI major bleeding included weight ≤65 kg (HR, 3.08; 95% CI, 1.74–5.43), hemoglobin ≤12 g/dL (HR, 5.72; 95% CI, 3.26–10.04), and estimated glomerular filtration rate <60 mL/min per 1.73 m 2 (HR, 3.68; 95% CI, 2.14–6.34).
- Discontinuing aspirin after 3 months while maintaining ticagrelor monotherapy reduced net adverse clinical events among patients harboring these bleeding risk factors (HR, 0.59; 95% CI, 0.39–0.90; P interaction =0.74).
Study Design
Type
RCT (n=2,660)
Blinding
Unblinded
Randomization
Randomly assigned to ticagrelor monotherapy after a 3-month DAPT regimen or a ticagrelor-based 12-month DAPT regimen
Multicenter
Yes
Structured PICO
Does 3-month aspirin therapy with continued ticagrelor reduce net adverse clinical events compared to 12-month dual antiplatelet therapy in ACS patients undergoing PCI?
P
Population
2,660 patients with acute coronary syndrome who underwent successful PCI with sirolimus-eluting stents, evaluated for bleeding risk factors and the effect of 3-month vs 12-month aspirin therapy over 12 months.
I
Intervention
Ticagrelor monotherapy after 3 months of dual antiplatelet therapy (3-month aspirin therapy with continued ticagrelor)
C
Comparator
Ticagrelor-based 12-month dual antiplatelet therapy (12-month aspirin and ticagrelor)
O
Outcome
Net adverse clinical event (composite of TIMI major bleeding and major adverse cardiac and cerebrovascular events) at 12 monthscomposite
Main Result
Hazard Ratio: 0.59 (95% CI 0.39–0.9)
Absolute Event Rate: 5% vs 8.6%
p-value: P interaction = 0.74
Early aspirin discontinuation (at 3 months) while continuing ticagrelor provides a net clinical benefit in ACS patients, even those with high bleeding risk factors.
Limitations
- Post hoc analysis design
- Exclusion of patients with prior stroke or thrombocytopenia
- Potential confounding by unmeasured variables like peripheral artery disease
- Explorative nature of transradial intervention effects
- Limited generalizability to non-Asian populations and other stent types
Key expert perspectives
Captured external expert commentary on this paper, strongest first. Original sources are linked where available.
“This finding indicates that ticagrelor monotherapy could be an optimal strategy, balancing both ischemic and bleeding risks for patients with ACS treated by ultrathin, biodegradable-polymer, sirolimus-eluting stents.”
DBDeepak BhattInterventional cardiologist, Brigham and Women's Hospital
“To have two independently done trials essentially reaching the same conclusion that this strategy of ticagrelor monotherapy essentially cuts major bleeding in half is very comforting. So I think that core finding is a true one.”
CDClaire DuvernoyCardiologist, University of Michigan
“This was a wonderfully done trial that adds to our expanding body of evidence for the newer, more potent P2Y12 inhibitors as monotherapy after PCI. This trial stands out because it was an all-ACS trial and, from what I can tell, the only such trial so far that had a significant population of patients with STEMI. The fact that there was no signal of harm in the STEMI subpopulation is very important.”
Implication
Supports shortening aspirin to 3 months with ticagrelor continuation in high-bleeding-risk ACS; extends randomized TICO evidence to patients with identified risk factors.
Abstract
Background There is a lack of data on factors that are related to clinically relevant bleeding after ticagrelor treatment. We investigated the clinical and procedural factors related to major bleeding in patients with acute coronary syndrome treated with ticagrelor after coronary stent implantation. Methods and Results From the TICO (Ticagrelor Monotherapy After 3 Months in Patients Treated With New Generation Sirolimus‐Eluting Stent for Acute Coronary Syndrome) randomized trial, a total of 2660 patients were included for the present study. Patients with major bleeding, defined by TIMI (Thrombolysis in Myocardial Infarction) major or Bleeding Academic Research Consortium type 3 or 5, were compared with those without major bleeding. On the basis of multivariable and receiver operating characteristic curve analyses, weight ≤65 kg, hemoglobin ≤12 g/dL, and estimated glomerular filtration rate <60 mL/min per 1.73 m 2 were associated with an increased risk of major bleeding. In contrast, 3‐month aspirin therapy with continued ticagrelor (versus 12‐month aspirin and ticagrelor) was associated with a decreased risk of major bleeding. The lower risk of a net adverse clinical event (a composite of TIMI major bleeding and major adverse cardiac and cerebrovascular events) in patients treated with 3‐month aspirin therapy reported from the TICO trial remained valid in patients with any of these risk factors (hazard ratio, 0.59; 95% CI, 0.39–0.90; P interaction =0.74). Conclusions Low body weight, anemia, and chronic kidney disease were risk factors for major bleeding after ticagrelor therapy. Early aspirin discontinuation had a net clinical benefit among patients with a bleeding risk. Registration URL: https://www.clinicaltrials.gov/ . Unique Identifier: NCT02494895.
Discussion
No takes yet. Share an insight, caveat, or question.
Cite This Study
Cho et al. (2021) conducted an RCT in Acute coronary syndrome treated with ticagrelor after coronary stent implantation (n=2,660). 3-month aspirin therapy with continued ticagrelor vs. 12-month aspirin and ticagrelor was evaluated on Net adverse clinical event (composite of TIMI major bleeding and major adverse cardiac and cerebrovascular events) in patients with bleeding risk factors (HR 0.59, 95% CI 0.39-0.90, p=P interaction = 0.74). In patients with acute coronary syndrome and bleeding risk factors, 3-month aspirin therapy with continued ticagrelor reduced net adverse clinical events by 41% compared to 12-month dual antiplatelet therapy (HR 0.59).